1. Field of the Invention
The present invention belongs to the field of medicine, particularly relates to the use of phenethyl caffeate derivatives in the preparation of a medicament against tumor angiogenesis.
2. Description of the Related Art
Angiogenesis refers to the process of forming new vessels continuously based on the existing vessels of tissues. Angiogenesis under physiological conditions can be found in the processes of embryonic development and wound healing. Under pathological conditions, angiogenesis mainly exists in tumor and chronic inflammatory diseases. Inhibition of tumor angiogenesis not only can inhibit the growth and reproduction of tumor cells, but also has inhibitory effect on the metastasis and recurrence of the tumor (Carmeliet P, Jain R K. 2000. Angiogenesis in cancer and other diseases. Nature, 407 (6801): 249-57).
Since the world's first anti-angiogenic drug (bevacizumab, with trade name of Avastin and produced by Genentech Inc. in USA) was approved by U.S. FDA for the treatment of tumor in 2004, in just a few years, there has been a dozen of such drugs, which have been approved respectively for marketing internationally in a number of countries. The number of drugs studied in Phase II or III clinical trial is more than 50 (Folkman J. 2007. Angiogenesis: an organizing principle for drug discovery? Nature Review Drug Discovery. 6(4): 273-86). The world's pharmaceutical giants have focused on the research and development of such drugs as such drugs can inhibit the growth of tumor effectively, have significantly-reduced toxic and side effects on patients compared to radiation and chemotherapy drugs, and can also inhibit the metastasis of tumor. Therefore, research and application of angiogenesis inhibitors provides a new anti-cancer means and way for clinical patients.
However, currently the main target of the drugs resisting rumor angiogenesis is the endothlial cell (EC) of the new vessel. Although damaging to endothlial cells can inhibit angiogenesis, the normal vessels of the body (non-tumor vessels) is also damaged inevitably, especially when patients suffering from tumor also have atherosclerosis, the drug with the vascular endothlial cell as a target often inevitably results in damaging to the vessels, inducing complications which threaten the life of patients, such as thrombosis. In fact, patients with tumor are often elderly, and the elderly are the high-risk group suffering from atherosclerosis. Thus, these side is effects of the existing drugs resisting tumor angiogenesis limit their clinical application.
Study found that, besides endothlial cells, there are other factors affecting the formation of vessels during the process of tumor angiogenesis, such as pericytes and matrix proteins required for angiogenesis, both of which are indispensable factors affecting tumor angiogenesis. Therefore, it is of important social significance and economic value to development a medicament which can inhibit tumor angiogenesis, without potentially inducing thrombosis in normal non-tumor tissues.